The aim of this work is to investigate the mechanisms controlling the expression of a multigene family, namely the class I MHC genes. It has been demonstrated that there are 6-8 class I genes in the genome of the miniature swine. The products of some of these genes are classical transplantation antigens, whereas the others are unknown. Although the transplantation antigens appear to be expressed on all somatic cells, the level of this expression varies. The patterns of expression of the remaining genes have not been analyzed. To address the question of the molecular regulation of the expression of this set of related genes, a series of genomic clones containing MHC-homologous DNA sequences has been isolated. Of the 6-8 genes in the genome, six have been isolated. The expression potential of these genes has been analyzed by transfection of mouse L cells. Two categories of MHC genes have been identified in this way: 1) a set of closely related genes which are expressed in L cells and appear to represent the genes encoding the classical transplantation antigens. These genes encode products which are expressed on the cell surface and are able to bind a monoclonal antibody which recognize a common determinant. 2) A set of more distantly related genes which are also expressed in L cells, but whose product is not recognized by the monoclonal antibody. Regulatory sequences within one of the SLA genes have been identified by generating a series of 5' end deletion mutants. Using such a set of mutants, the positions of the transcriptional promoter and interferon - enhancer have been mapped. Other segments of the class I gene are also being analyzed for the presence of other regulatory sequences. The patterns of expression of the various class I genes in vivo has also been analyzed. Large variations in the level of expression are observed among different tissues for all of the genes. Representative genes from each of the two class I gene sub-groups appear to have similar patterns of expression.